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Common denominator genes that distinguish colorectal carcinoma from normal mucosa

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Microarray technology has been used by a growing number of investigators and several studies have been published that list hundreds of genes differentially expressed by colorectal carcinoma (CRC) and normal mucosa (MC). On the basis of our own and other investigators’ microarray data, our goal was to identify a common denominator gene cluster distinguishing CRC from MC.

Methods

Thirty GeneChips (HG-U133A, Affymetrix) were hybridized, 20 with RNA of CRC stages I–IV (UICC) and 10 with MC. Expression signals showing at least a 4-fold difference between CRC and MC (p<0.01) were identified as differentially expressed. In addition, in our integrative data analysis approach only those genes whose expression was altered simultaneously in at least 2 of 5 recently published studies were subjected to an unsupervised hierarchical cluster analysis.

Results

We detected 168 up- and 283 down-regulated genes in CRC relative to MC. Twenty-three genes were filtered from the five articles reviewed. An unsupervised hierarchical cluster analysis of these 23 genes confirmed the high specificity of these genes to differentiate between CRC and MC in our microarray data.

Conclusions

Colorectal cancer and mucosa could be clearly separated by 23 genes selected for being differentially expressed more than once in a recent literature review. These genes represent a common denominator gene cluster that can be used to distinguish colorectal MC from CRC.

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References

  1. Leslie A, Carey FA, Pratt NR, Steele RJ (2002) The colorectal adenoma–carcinoma sequence. Br J Surg 89:845–860

    Article  CAS  PubMed  Google Scholar 

  2. Cho KR, Vogelstein B (1992) Genetic alterations in the adenoma–carcinoma sequence. Cancer 70 [Suppl]:1727–1731

    CAS  PubMed  Google Scholar 

  3. Arends JW (2000) Molecular interactions in the Vogelstein model of colorectal carcinoma. J Pathol 190:412–416

    Article  CAS  PubMed  Google Scholar 

  4. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532

    CAS  PubMed  Google Scholar 

  5. Hermanek P, Sobin LH, Wittekind C (1999) How to improve the present TNM staging system. Cancer 86:2189–2191

    CAS  PubMed  Google Scholar 

  6. Notterman DA, Alon U, Sierk AJ, Levine AJ (2001) Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays. Cancer Res 61:3124–3130

    CAS  PubMed  Google Scholar 

  7. Kitahara O, Furukawa Y, Tanaka T, Kihara C, Ono K, Yanagawa R, Nita ME, Takagi T, Nakamura Y, Tsunoda T (2001) Alterations of gene expression during colorectal carcinogenesis revealed by cDNA microarrays after laser-capture microdissection of tumor tissues and normal epithelia. Cancer Res 61:3544–3549

    CAS  PubMed  Google Scholar 

  8. Birkenkamp-Demtroder K, Christensen LL, Olesen SH, Frederiksen CM, Laiho P, Aaltonen LA, Laurberg S, Sorensen FB, Hagemann R, Orntoft TF (2002) Gene expression in colorectal cancer. Cancer Res 62:4352–4363

    CAS  PubMed  Google Scholar 

  9. Takemasa I, Higuchi H, Yamamoto H, Sekimoto M, Tomita N, Nakamori S, Matoba R, Monden M, Matsubara K (2001) Construction of preferential cDNA microarray specialized for human colorectal carcinoma: molecular sketch of colorectal cancer. Biochem Biophys Res Commun 285:1244–1249

    Article  CAS  PubMed  Google Scholar 

  10. Williams NS, Gaynor RB, Scoggin S, Verma U, Gokaslan T, Simmang C, Fleming J, Tavana D, Frenkel E, Becerra C (2003) Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference. Clin Cancer Res 9:931–946

    CAS  PubMed  Google Scholar 

  11. Croner RS, Guenther K, Foertsch T, Siebenhaar R, Brueckl WM, Stremmel C, Hlubek F, Hohenberger W, Reingruber B (2004) Tissue preparation for gene expression profiling of colorectal carcinoma: three alternatives to laser microdissection with preamplification. J Lab Clin Med 143:344–351

    Article  CAS  PubMed  Google Scholar 

  12. Nachamkin I, Panaro NJ, Li M, Ung H, Yuen PK, Kricka LJ, Wilding P (2001) Agilent 2100 bioanalyzer for restriction fragment length polymorphism analysis of the Campylobacter jejuni flagellin gene. J Clin Microbiol 39:754–757

    Article  CAS  PubMed  Google Scholar 

  13. Hsiao LL, Dangond F, Yoshida T, Hong R, Jensen RV, Misra J, Dillon W, Lee KF, Clark KE, Haverty P, Weng Z, Mutter GL, Frosch MP, Macdonald ME, Milford EL, Crum CP, Bueno R, Pratt RE, Mahadevappa M, Warrington JA, Stephanopoulos G, Stephanopoulos G, Gullans SR (2001) A compendium of gene expression in normal human tissues. Physiol Genomics 7:97–104

    CAS  PubMed  Google Scholar 

  14. Durig J, Nuckel H, Huttmann A, Kruse E, Holter T, Halfmeyer K, Fuhrer A, Rudolph R, Kalhori N, Nusch A, Deaglio S, Malavasi F, Moroy T, Klein-Hitpass L, Duhrsen U (2003) Expression of ribosomal and translation-associated genes is correlated with a favorable clinical course in chronic lymphocytic leukemia. Blood 101:2748–2755

    Article  CAS  PubMed  Google Scholar 

  15. Guenzi E, Topolt K, Lubeseder-Martellato C, Jorg A, Naschberger E, Benelli R, Albini A, Sturzl M (2003) The guanylate binding protein-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expression. EMBO J 22:3772–3782

    Article  CAS  PubMed  Google Scholar 

  16. Lubeseder-Martellato C, Guenzi E, Jorg A, Topolt K, Naschberger E, Kremmer E, Zietz C, Tschachler E, Hutzler P, Schwemmle M, Matzen K, Grimm T, Ensoli B, Sturzl M (2002) Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases. Am J Pathol 161:1749–1759

    CAS  PubMed  Google Scholar 

  17. Hiki Y, Iyama K, Tsuruta J, Egami H, Kamio T, Suko S, Naito I, Sado Y, Ninomiya Y, Ogawa M (2002) Differential distribution of basement membrane type IV collagen alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV) chains in colorectal epithelial tumors. Pathol Int 52:224–233

    Article  CAS  PubMed  Google Scholar 

  18. Shiozawa J, Ito M, Nakayama T, Nakashima M, Kohno S, Sekine I (2000) Expression of matrix metalloproteinase-1 in human colorectal carcinoma. Mod Pathol 13:925–933

    Article  CAS  PubMed  Google Scholar 

  19. Kim PJ, Plescia J, Clevers H, Fearon ER, Altieri DC (2003) Survivin and molecular pathogenesis of colorectal cancer. Lancet 362:205–209

    Article  CAS  PubMed  Google Scholar 

  20. Takemasa I, Yamamoto H, Sekimoto M, Ohue M, Noura S, Miyake Y, Matsumoto T, Aihara T, Tomita N, Tamaki Y, Sakita I, Kikkawa N, Matsuura N, Shiozaki H, Monden M (2000) Overexpression of CDC25B phosphatase as a novel marker of poor prognosis of human colorectal carcinoma. Cancer Res 60:3043–3050

    CAS  PubMed  Google Scholar 

  21. Miwa N, Furuse M, Tsukita S, Niikawa N, Nakamura Y, Furukawa Y (2000) Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers. Oncol Res 12:469–476

    CAS  PubMed  Google Scholar 

  22. Li A, Varney ML, Singh RK (2001) Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials. Clin Cancer Res 7:3298–3304

    CAS  PubMed  Google Scholar 

  23. Mason IJ, Taylor A, Williams JG, Sage H, Hogan BL (1986) Evidence from molecular cloning that SPARC, a major product of mouse embryo parietal endoderm, is related to an endothelial cell ‘culture shock’ glycoprotein of Mr 43,000. EMBO J 5:1465–1472

    CAS  PubMed  Google Scholar 

  24. Lewin AR, Reid LE, McMahon M, Stark GR, Kerr IM (1991) Molecular analysis of a human interferon-inducible gene family. Eur J Biochem 199:417–423

    CAS  PubMed  Google Scholar 

  25. Lincoln AJ, Wickramasinghe D, Stein P, Schultz RM, Palko ME, De Miguel MP, Tessarollo L, Donovan PJ (2002) Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation. Nat Genet 30:446–449

    Google Scholar 

  26. Dhanesuan N, Sharp JA, Blick T, Price JT, Thompson EW (2002) Doxycycline-inducible expression of SPARC/osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition. Breast Cancer Res Treat 75:73–85

    Article  CAS  PubMed  Google Scholar 

  27. Behrens P, Brinkmann U, Wellmann A (2003) CSE1L/CAS: its role in proliferation and apoptosis. Apoptosis 8:39–44

    Article  CAS  PubMed  Google Scholar 

  28. Payne AM, Downes SM, Bessant DA, Plant C, Moore T, Bird AC, Bhattacharya SS (1999) Genetic analysis of the guanylate cyclase activator 1B (GUCA1B) gene in patients with autosomal dominant retinal dystrophies. J Med Genet 36:691–693

    CAS  PubMed  Google Scholar 

  29. Puscas I, Coltau M, Baican M, Domuta G, Hecht A (2001) Calcium, carbonic anhydrase and gastric acid secretion. Physiol Res 50:359–364

    CAS  PubMed  Google Scholar 

  30. Makela S, Kere J, Holmberg C, Hoglund P (2002) SLC26A3 mutations in congenital chloride diarrhea. Human Mutat 20:425–438

    Article  CAS  Google Scholar 

  31. Sweadner KJ, Rael E (2000) The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression. Genomics 68:41–56

    Article  CAS  PubMed  Google Scholar 

  32. Sly WS, Whyte MP, Sundaram V, Tashian RE, Hewett-Emmett D, Guibaud P, Vainsel M, Baluarte HJ, Gruskin A, Al-Mosawi Met al (1985) Carbonic anhydrase II deficiency in 12 families with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. N Engl J Med 313:139–145

    Google Scholar 

  33. Schweinfest CW, Henderson KW, Suster S, Kondoh N, Papas TS (1993) Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas. Proc Natl Acad Sci USA 90:4166–4170

    Google Scholar 

  34. Stoehlmacher J, Lenz HJ (2003) Implications of genetic testing in the management of colorectal cancer. Am J Pharmacogenomics 3:73–88

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was sponsored by the German Federal Ministry for Education and Science (BMBF) within the National Genome Science Network (NGFN).

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Authors and Affiliations

  1. Department of Surgery, University of Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Roland S. Croner, Thomas Foertsch, Klaus Guenther, Renate Siebenhaar, Christian Stremmel, Klaus E. Matzel, Werner Hohenberger & Bertram Reingruber

  2. 1st Department of Internal Medicine, University of Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Wolfgang M. Brueckl

  3. Institute of Pathology, University of Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Thomas Papadopoulos & Thomas Kirchner

  4. Department of Experimental Medicine II, University of Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Jürgen Behrens

  5. Institute of Cell Biology, University of Essen, Germany

    Ludger Klein-Hitpass

  6. Department of Molecular and Experimental Surgery, University of Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Michael Stuerzl

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  1. Roland S. Croner
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  2. Thomas Foertsch
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Correspondence to Roland S. Croner.

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Croner, R.S., Foertsch, T., Brueckl, W.M. et al. Common denominator genes that distinguish colorectal carcinoma from normal mucosa. Int J Colorectal Dis 20, 353–362 (2005). https://doi.org/10.1007/s00384-004-0664-7

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  • DOI: https://doi.org/10.1007/s00384-004-0664-7

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